NEWS: Genes tied to abnormal immune response in mice with lupus

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Public release date: 14-Dec-2004

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Cell Press

Genes tied to abnormal immune response in mice with lupus

Scientists have uncovered a link between a family of genes and abnormalities

of the immune system that are associated with systemic lupus erythematosus

(SLE), a devastating disease that affects over 1 million Americans. The

research, published in the December issue of Immunity, significantly

advances the understanding of the pathology of lupus-like autoimmunity in

mice and may facilitate the design of future therapies for lupus in humans.

A normal immune system protects the body against viruses, bacteria and other

potentially harmful foreign invaders. In an autoimmune disease, like SLE,

the immune system loses its ability to tell the difference between foreign

substances that pose a threat and the cells of the body. In SLE, the immune

system attacks and damages the body's own tissues and organs, including the

joints, kidneys, heart, lungs, brain, blood and skin. Dr. K. Wakeland

from the University of Texas Southwestern Medical Center and colleagues used

a lupus-prone mouse model of SLE to characterize genes directly involved

with SLE susceptibility.

The researchers report that variations in the structure and expression of a

subset of genes belonging to the SLAM/CD2 family may contribute to

autoimmunity in mice with lupus. Scientists have known for some time that

SLAM/CD2 genes play a critical role in controlling immune cells and

responses. Evidence presented here suggests that the altered SLAM/CD2

members may be responsible for abnormal lymphocyte responses. The Ly108

gene, which is expressed at elevated levels in lymphocytes from lupus

susceptible mice, has emerged as a likely contributor to abnormal immune

activation. However, Ly108 and other SLAM/CD2 genes are thought to act in

combination with additional genes and signaling molecules in these mice and

further research is needed to identify the specific interactions that lead

to an overzealous immune response.

The researchers conclude that sequence and expression level differences in a

subset of SLAM/CD2 genes are associated with the autoimmune response

observed in SLE mice. " Given our association of variations in the SLAM/CD2

cluster with lupus susceptibility in mice, further work on the relationship

of polymorphisms in the SLAM/CD2 cluster to SLE in humans is clearly

warranted, " says Dr. Wakeland.

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Amy E. Wandstrat, Nguyen, Nisha Limaye, Alice Y. Chan, Srividya

Subramanian, Xiang-Hong Tian, Young-Sun Yim, Pertsemlidis, Harold

R. Garner, Jr., ce Morel, and K. Wakeland: " Association of

Extensive Polymorphisms in the SLAM/CD2 Gene Cluster with Murine Lupus "

Publishing in Immunity, Volume 21, Number 6, December 2004, pages 769­780.

http://www.immunity.com

The other members of the research team include Amy E. Wandstrat,

Nguyen, Nisha Limaye, Alice Y. Chan, Srividya Subramanian, Xiang-Hong Tian,

Pertsemlidis, and Harold R. Garner, Jr. of University of Texas

Southwestern Medical Center; Young-Sun Yim of the University of Missouri;

and ce Morel of the University of Florida School of Medicine.

This work was supported by grants from the National Institutes of Health

(NIH), The Alliance for Lupus Research, The Lupus Research Institute, and

the Arthritis Foundation (E.K.W.). A.E.W. was supported by an NIH

postdoctoral fellowship and by a grant from the Lupus Foundation. N.L. was

supported in part by a grant from the National Institute of Allergy and

Infectious Disease, T32AI005284.

The context and implications of this work are discussed in a Preview by

S. Wicker and ce B. .